MOLECULAR BIOLOGY AND VIRULENCE OF CTX PHAGE

描述(改编自申请者的摘要)：霍乱毒素是 革兰氏阴性菌霍乱弧菌的主要毒力因子 这会导致严重的腹泻疾病霍乱。调查人员 最近发现这种强效肠毒素是由一种新的 丝状噬菌体，命名为CTX。CTX噬菌体是第一个 已知的丝状噬菌体可导致宿主的溶原性转换 细菌。CTX噬菌体可以整合到霍乱弧菌的染色体上，并 形成稳定的溶原物，或在诱导后，从染色体上切除 以质粒的形式复制。在噬菌体的这个复制阶段 生活周期中，霍乱毒素可以独立表达的因素 它们被认为是其表达所必需的。我们的演示 霍乱弧菌溶原菌CTX噬菌体在宿主体内的诱导 胃肠道提示体内CTX噬菌体有可能 诱导对霍乱弧菌的毒力有重要作用。 拟议研究的目标是了解 在分子水平上的CTX噬菌体，并评估这一意义 噬菌体在霍乱发病机制中的作用。这些研究将确定 毒力水平传递机制的分子生物学 基因，从而加深了我们对病原体出现的理解。 溶原菌CTX噬菌体肠道内诱导的研究 建立理解表达调控的新范式 在各种细菌病原体中编码毒力因子的噬菌体 是通过转化噬菌体进行溶原化的。这项工作也将具有重要的意义 设计更安全的霍乱弧菌减毒活疫苗的分支 菌株。

DESCRIPTION (Adapted from the applicant's abstract): Cholera toxin is the principal virulence factor of Vibrio cholerae, the Gram-negative bacterium that causes the severe diarrheal disease cholera. The investigators recently discovered that this potent enterotoxin is encoded by a novel filamentous bacteriophage designated CTX. The CTX phage is the first filamentous phage known to result in the lysogenic conversion of a host bacterium. The CTX phage can integrate into the V. cholerae chromosome and form stable lysogens or, after induction, excise from the chromosome and replicate as a plasmid. During this replicative stage of the phage life-cycle, cholera toxin can be expressed independently of the factors which were believed to be essential for its expression. Our demonstration of the induction of CTX phage from V. cholerae lysogens within the host gastrointestinal tract suggests the possibility that in vivo CTX phage induction plays a significant role in the virulence of V. cholerae. The objectives of the proposed studies are to understand the life-cycle of the CTX phage at the molecular level and to assess the significance of this bacteriophage in the pathogenesis of cholera. These studies will establish the molecular biology of a mechanism of horizontal transfer of virulence genes and thereby further our understanding of the emergence of pathogens. The study of the intraintestinal induction of CTX phage from lysogens, could establish a new paradigm for understanding the regulation of the expression of phage encoded virulence factors in a variety of bacterial pathogens that are lysogenized with converting phage. This work will also have important ramifications for the design of safer live attenuated V. cholerae vaccine strains.